Roles of Mitochondrial Quality Control in the Pathogenesis of Atherosclerosis

Mitochondrial quality control (MQC) mechanisms – including biogenesis, dynamics, mitophagy, proteostasis, the unfolded protein response, and mitochondrial-derived vesicles – play critical roles in the development of atherosclerosis. Dysregulation of these processes can lead to mitochondrial dysfunction, and subsequently the initiation of a pathological cascade characterized by oxidative stress, chronic inflammation, and the accumulation of lipids within arterial walls. Specifically, ROS overproduction and redox state imbalance are key molecular aspects that exacerbate mitochondrial damage, and create a self-perpetuating cycle of cellular injury and disease progression. Emerging therapeutic strategies targeting the modulation of MQC have promise in attenuating atherosclerotic progression by restoring mitochondrial biogenesis, restoring the balance of fusion and fission dynamics, enhancing the clearance of damaged mitochondria, and improving protein homeostasis. Advancing understanding of the molecular regulators and protein interaction networks within MQC pathways might facilitate the development of precision-targeted therapies. However, substantial challenges persist in translating these insights into clinical applications. This review explores the relationship between MQC mechanisms and atherosclerosis, focusing on the associated pathways and potential avenues for therapeutic intervention.